Stability difference of disulfide-containing prodrugs in incubations with GSH, cysteine, or human and rat whole blood
| Compound | % Disulfide Remaining | |||
|---|---|---|---|---|
| GSH, 4.0 mMa | Cysteine, 30 µMa | Rat Whole Bloodb | Human Whole Bloodb | |
| 3 | 56 | 100 | 0.1 | 5 |
| 4 | 21 | 99 | 0.3 | 24 |
| 5 | 68 | 100 | 5 | 80 |
| 6 | 44 | 98 | 1 | 45 |
| 7 | 88 | 100 | 87 | 120 |
| 8 | 100 | 100 | 19 | 120 |
| 9 | 100 | 100 | 100 | 108 |
| 10 | 82 | 99 | 124 | 124 |
↵a Disulfide cleavage in presence of indicated concentration of GSH or cysteine at 24 hours. See the Supplemental Information for additional details.
↵b Disulfide was incubated with whole blood, and aliquots were analyzed at 24 hours. Procaine (10 µM) was used as the positive-control incubation with <3% remaining after 24 hours.